Human Cytomegalovirus Infection of Human Hepatic Sinusoidal Endothelial Cells Modulates T Cell Recruitment into the Liver
Final Report Abstract
Human Cytomegalovirus (HCMV) infection is associated with an increased morbidity after liver transplantation by facilitating allograft rejection and accelerating underlying hepatic inflammation. Hepatic sinusoidal endothelial cells (HSEC) control lymphocyte recruitment into the liver, fulfil immune regulatory functions and have been identified as targets of murine CMV and the source of latency and reactivation. We hypothesized that HCMV infection of human HSEC will modulate the ability to recruit and activate allogeneic T cells thereby providing a mechanism to explain how HCMV infection increases hepatic immune activation. We could demonstrate that HCMV infection of primary human HSEC facilitates ICAM-1 and CXCL10-dependent CD4 T cell transendothelial migration under physiological levels of shear stress. Recruited T cells were primarily CXCR3-high effector memory T cells that demonstrated features of Th1 activation after migration. In parallel, regulatory T cells were stronger recruited via infected HSEC and maintained a suppressive phenotype after migration. Our data contributed to understand how CMV infection facilitates hepatic inflammation and immune activation and may simultaneously favour CMV persistence.
Publications
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Soluble urokinase plasminogen activator receptor (suPAR) is compartmentally regulated in decompensated cirrhosis and indicates immune activation and short-term mortality. JIntern Med 2013;274(1):86-100
Zimmermann HW, Reuken PA, Koch A, Bartneck M, Adams DH, Trautwein C, Stallmach A, Tacke F, Bruns T
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NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis. Liver Int 2012; 32(2):223-30
Bruns T, Peter J, Reuken P, Grabe D, Schuldes S, Brenmoehl J, Schölmerich J, Wiest R, Stallmach A
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Recruitment mechanisms of primary and malignant B cells to the human liver. Hepatology 2012;56:1521-1531
Shetty S, Bruns T, Weston CJ, Stamataki Z, Oo YH, Long HM, Reynolds GM, Pratt G, Moss P, Jalkanen S, Hubscher SG, Lalor PF, Adams DH
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Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response. J Hepatol. 2014
Trivedi PJ, Bruns T, Cheung A, Li KK, Kittler C, Kumagi T, Shah H, Corbett C, Al-Harthy N, Acarsu U, Coltescu C, Tripathi D, Stallmach A, Neuberger J, Janssen HL, Hirschfield GM
